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Biomedical subjects

C Zimmer

Publications and source records attributed to C Zimmer.

At least 19 recordsLinked to original sources

Voxel-based morphometry indicates relative preservation of the limbic prefrontal cortex in early Huntington disease.

In Huntington disease (HD), both the genetic defect and mutant gene product huntington are known but the exact mechanisms that lead to neuronal loss are poorly understood. Until now, the distribution of tissue loss throughout the brain has been investigated intensively. Here we searched for areas that, antipodal to the striatum, display grey-matter (GM) preservation. We performed high resolution T1-weighted magnetic resonance imaging and voxel-based morphometry in 46 patients in early HD and 46 healthy controls. We applied an analysis of covariance (ANCOVA) model with the total GM volume of each participant as covariate. In accordance with earlier reports, group comparisons revealed GM decrease in the striatum, insula, and thalamus as well as in dorsolateral frontal and occipital areas. In contrast, the limbic prefrontal cortex displayed GM preservation. Our findings support hypotheses that postulate differential involvement of frontosubcortical circuits in the pathophysiology of HD.

Adult↗

[Cerebral lesions in acute arterial hypertension: the characteristic MRI in hypertensive encephalopathy].

PURPOSE: In the nine years since the posterior reversible (leuc) encephalopathy syndrome (PRES) was first described, a number of causes have been under discussion. These not only include arterial hypertension, i. e. hypertensive crises, but also various toxic substances, i. e. immunosuppressive or chemotherapeutic agents, that are responsible for the formation of the symptoms and characteristic MR tomographic brain findings. MATERIALS AND METHODS: Initial and follow-up MRI examinations of 8 patients were analyzed. All patients had acute neurological symptoms (headaches, seizures, visual disorders and vigilance disturbances) together with a detectable hypertensive crisis. RESULTS: MRI disclosed increased signal intensity in subcortical and some cortical lesions in all patient FLAIR sequences. These changes were particularly extensive in the posterior circulation (occipital, cerebellum and brain stem) although they were also detected in brain areas supplied by the carotid artery. However, a cytotoxic genesis of the changes was ruled out in each patient by means of a normal DWI. Furthermore, when the blood pressure was normalized, reversibility of the lesions as proof of the diagnosis was detectable. CONCLUSION: The imaging findings can be typically analyzed as a predominantly posterior distribution of encephalopathic lesions with a high probability of reversibility after lowering blood pressure was patients suffering from a critical increase in blood pressure with corresponding neurological symptoms. The exact pathophysiology remains unclear, but the cause currently most favored is a vasculopathy of the posterior circulation due to diminished adrenergic autoregulation in combination with a dysfunction of the endothelial cells. In conclusion, we suggest designating this subpopulation from the non-uniform pool of patients with posterior (leuc) encephalopathy as "hypertensive encephalopathy". "Hypertensive encephalopathy" has to be distinguished from "toxic encephalopathy", particularly due to different therapeutic and prognostic consequences.

Adult↗

Profound midbrain atrophy in patients with Wilson's disease and neurological symptoms?

Wilson's disease (WD) is characterized by impaired hepatic copper secretion and subsequent copper accumulation in many organs predominantly liver and brain, secondary to loss of function mutations in the copper transport protein ATP7B. If the disease is recognized too late or treatment is not adequate, brain copper accumulation leads to progressive neurodegeneration with a variety of clinical symptoms. The nigrostriatal dopaminergic system seems rather vulnerable. Midbrain atrophy, however, has not been recognized as one of the prime features of patients with WD. Here we report quantification of midbrain diameter in 41 patients with WD. Data were correlated to the severity of neurological symptoms and the integrity of dopaminergic neurons measured via dopamine transporter binding. For control, we measured midbrain diameter in 18 patients with no evidence for brainstem dysfunction and 5 patients with progressive supranuclear palsy (PSP). Patients with WD had a reduced midbrain diameter (15.5 +/- 0.4 mm) compared to controls (18.5 +/- 0.2 mm). WD patients without neurological symptoms had midbrain diameter that were not different from controls (18.0 +/- 0.3 mm), while patients with neurological symptoms showed midbrain atrophy similar to patients with PSP (14.4 +/- 0.3 mm versus 14.1 +/- 0.3). There was a strong and significant correlation between midbrain atrophy and the severity of neurological symptoms (r= -0.68, p < 0.001) while midbrain atrophy and dopamine transporter binding correlated significantly but was less pronounced (r=0.46, p < 0.001). In summary, we were able to show, that midbrain diameter is an easy to perform quantification of neurodegeneration induced by brain copper accumulation and that other structures than substantia nigra dopaminergic neurons seem to contribute to midbrain atrophy in WD.

Adult↗

[Causal illness attributions and healthcare utilization in fibromyalgia syndrome].

INTRODUCTION: High utilization of medical services has been described for patients with fibromyalgia syndrome (FMS). There are no studies available that assess whether the patients' subjective illness beliefs influence their behavior in utilizing healthcare. METHODS: Examinations were performed by taking the history of pain treatment in 100 FMS patients evaluated by experts for the social court and 25 patients attending an outpatient pain center. The subjective illness theories were drawn from the patients' responses to the German Pain Questionnaire (GPQ). The statements made on the GPQ regarding utilization of healthcare services were compared with the records and the answers given in the interview on pain therapy. RESULTS: Of the patients, 44% specified a somatic, 2% a psychogenic, 9% none, and 45% a psychosomatic illness belief. The patients were classified as high utilizers of specialized medical services in 25% of the cases and of psychiatric-psychotherapeutic services in 14%. No significant correlations between the type of subjective illness theory and utilization of specialized medical or psychiatric-psychotherapeutic services were observed. CONCLUSION: From the psychosomatic viewpoint, only part of the FMS patients exhibited an inordinately one-sided somatic illness belief. The utilization of healthcare services cannot be explained by the subjective perception of the illness.

Attitude to Health↗

Glioma assessment using quantitative blood volume maps generated by T1-weighted dynamic contrast-enhanced magnetic resonance imaging: a receiver operating characteristic study.

PURPOSE: To investigate the use of blood volume maps in the non-invasive separation of glioma grades. MATERIAL AND METHODS: T1-weighted quantitative dynamic contrast-enhanced magnetic resonance imaging was used to quantify the fractional intratumoral blood volume of 41 gliomas (World Health Organization (WHO) grades II-IV). Two methods, mean fractional intratumoral blood volume determination and a system based on thresholds for extracting the tumor pixels with the highest vascularization from the blood volume maps, were investigated by means of receiver operating characteristic (ROC) analysis. The thresholds were adjusted using the ROC curve area calculated using the trapezoid method. RESULTS: The ability to separate grade II (WHO) gliomas from grades III-IV was nearly the same for both methods (ROC curve area 0.941 (threshold) versus 0.932 (mean value)) and significantly greater than the ability to separate grade IV (WHO) gliomas from grades II-III (ROC curve area 0.792 (threshold) versus 0.787 (mean value)). The best correspondence with WHO glioma grading was achieved using thresholds corresponding to only the 5.2% of tumor voxels with the largest blood volume for separating grade II gliomas and 4% for separating grade IV gliomas. CONCLUSION: Use of the optimized threshold resulted in matching with the WHO grading system in 74% of cases.

Adolescent↗

Cerebellar hypoplasia and quadrupedal locomotion in humans as a recessive trait mapping to chromosome 17p.

BACKGROUND: Congenital hereditary non-progressive hypoplasia of the cerebellum is a rare condition, frequently associated with other neuropathology such as lissencephaly. Clinically, the condition is associated with variable degrees of mental retardation, microcephaly, seizures, and movement disorders due to ataxia. In severe cases, patients are unable to ambulate independently, but nevertheless do use bipedal locomotion. METHODS AND RESULTS: Here we present a family with seven affected members, five of whom never learned to walk on two legs but have fully adapted to quadrupedal palmigrade locomotion. These subjects show signs of cerebellar ataxia and are mentally retarded. MRI analysis demonstrated hypoplasia of the cerebellum and the cerebellar vermis as well as a small nucleus dentatus and a thin corpus callosum but no other malformations. We show, by a genome-wide linkage scan, that quadrupedal locomotion is a recessive trait linked to chromosome 17p. CONCLUSIONS: Our findings have implications for understanding the neural mechanism mediating bipedalism, and, perhaps, the evolution of this unique hominid trait.

Adaptation, Physiological↗

Multiple sclerosis coinciding with Machado-Joseph disease.

Although inflammatory demyelination is considered to be the key feature in multiple sclerosis (MS) pathogenesis, histopathological investigations and MRI studies recently highlighted the extent of neuronal damage that occurs even in the early stages of the disease. We report the unusual case of a patient with Machado-Joseph disease (MJD; spinocerebellar ataxia (SCA) III) and discuss this coincidence in light current pathogenetic paradigms of CNS autoimmunity.

Adult↗

[Preoperative mapping of speech-eloquent areas with functional magnetic resonance imaging (fMRI): comparison of different task designs].

PURPOSE: Functional magnetic resonance imaging (fMRI) is a well-established, non-invasive method for pre-operative mapping of speech-eloquent areas. This investigation tests three simple paradigms to evaluate speech lateralisation and visualisation of speech-eloquent areas. MATERIALS AND METHODS: 14 healthy volunteers and 16 brain tumour patients were given three tasks: to enumerate months in the correct order (EM), to generate verbs fitting to a given noun (GV) and to generate words fitting to a given alphabetic character (GW). We used a blocked design with 80 measurements which consisted of 4 intervals of speech activation alternating with relaxation periods. The data were analysed on the basis of the general linear model using Brainvoyager(R). The activated clusters in the inferior frontal (Broca) and the posterior temporal (Wernicke) cortex were analysed and the laterality indices calculated. RESULTS: In both groups the paradigms GV and GW activated the Broca's area very robustly. Visualisation of the Wernicke's area was best achieved by the paradigm GV. The paradigm EM did not reliably stimulate either the frontal or the temporal cortex. Frontal lateralisation was best determined by GW and GV, temporal lateralisation by GV. CONCLUSION: The paradigms GV and GW visualise two essential aspects of speech processing: semantic word processing and word production. In a clinical setting with brain tumour patients, both, GV and GW can be used to visualise frontal and temporal speech areas, and to determine speech dominance.

Adult↗

Brain activation responses to subliminal or supraliminal rectal stimuli and to auditory stimuli in irritable bowel syndrome.

Visceral hypersensitivity in irritable bowel syndrome (IBS) has been associated with altered cerebral activations in response to visceral stimuli. It is unclear whether these processing alterations are specific for visceral sensation. In this study we aimed to determine by functional magnetic resonance imaging (fMRI) whether cerebral processing of supraliminal and subliminal rectal stimuli and of auditory stimuli is altered in IBS. In eight IBS patients and eight healthy controls, fMRI activations were recorded during auditory and rectal stimulation. Intensities of rectal balloon distension were adapted to the individual threshold of first perception (IPT): subliminal (IPT -10 mmHg), liminal (IPT), or supraliminal (IPT +10 mmHg). IBS patients relative to controls responded with lower activations of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) to both subliminal and supraliminal stimulation and with higher activation of the hippocampus (HC) to supraliminal stimulation. In IBS patients, not in controls, ACC and HC were also activated by auditory stimulation. In IBS patients, decreased ACC and PFC activation with subliminal and supraliminal rectal stimuli and increased HC activation with supraliminal stimuli suggest disturbances of the associative and emotional processing of visceral sensation. Hyperreactivity to auditory stimuli suggests that altered sensory processing in IBS may not be restricted to visceral sensation.

Acoustic Stimulation↗

Detection of an aneurysm of the vein of Galen following signs of cardiac overload in a 22-week old fetus.

OBJECTIVES: To present early prenatal diagnosis of an aneurysm of the Vein of Galen by detecting signs of cardiac overload in a 22-week old fetus. CASE: We report on a 22-week old fetus presenting with dilation of the heart, tricuspid and mitral valve regurgitation, reversed flow in the aortic arch and dilated neck vessels. Evaluation of the fetal brain revealed a dilated left ventricle, signs of brain hemorrhage and an anechoic structure between the two hemispheres. METHODS: By using the conventional Doppler technique, an intracerebral fistula and dilated vein of Galen was visualized. The complex vascular structure was demonstrated using 3-D color power angiography (3-D CPA). To our knowledge, this is the earliest diagnosis of this vascular malformation. CONCLUSION: Although signs of cardiac overload rarely appear before the third trimester in cases of arteriovenous fistulae, it was shown that these signs could lead to the correct diagnosis of an aneurysm of the vein of Galen. Additionally, we show that 3-D CPA is a promising technique to visualize complex vascular structures and make them easier to understand.

Abortion, Eugenic↗

[Cortisol/creatinine ratio in urine (UCC) of healthy cats].

In 31 healthy cats urine samples were taken to determine the cortisol/creatinine ratio (UCC) during hospitalisation and at home. The UCC of the samples, which had been taken in the clinic, was significantly higher (0-19 x 10(-6), Median 3 x 10(-6)) than the one of the samples taken at home (0-4 x 10(-6), Median 1 x 10(-6)). The parameter was neither influenced by the cat's age, sex or the fact that the cat stayed inside or outside, nor by the degree of visible agitation. Assay validation achieved good results regarding precision and accuracy of the measuring of cortisol and creatinine in the urine. The study shows that stress--caused by the visit to the veterinarian--can provoke a significant increase of UCC. Therefore, the parameter should be determined only from urine samples taken at home. Furthermore, it is important to notice that cortisol metabolites are measured in varying degree with the different assays. Therefore, it is inevitable that each laboratory generates its own reference values.

Animals↗

Enantiomeric determination of amlodipine in human plasma by liquid chromatography coupled to tandem mass spectrometry.

A sensitive method for the separation and determination of amlodipine enantiomers in plasma has been developed based on solid-phase extraction (SPE) with disposable extraction cartridges (DECs) in combination with chiral liquid chromatography (LC). The SPE technique is used to isolate the drug from the biological matrix and to prepare a cleaner sample before injection and analysis by HPLC coupled to mass spectrometry. The DEC is filled with ethyl silica (50 mg) and is first conditioned with a 2.5% ammonia in methanol solution and then with ammonium acetate buffer. A 1.0-ml volume of plasma is then applied on the DEC. The washing step is first performed with ammonium acetate buffer and secondly with a mixture of water and methanol (65:35, v/v), while the final elution step is obtained by dispensing methanol containing 2.5% of ammonia. The eluate is then collected and evaporated to dryness before being dissolved in the LC mobile phase and injected into the LC system. The stereoselective analysis of amlodipine is achieved on a Chiral AGP column containing alpha(1)-acid glycoprotein as chiral selector by using a mobile phase consisting of a 10-mM acetate buffer (pH 4.5) and 1-propanol (99:1, v/v). The LC system is coupled to tandem mass spectrometry with an APCI interface in the positive-ion mode. The chromatographed analytes are detected in the selected reaction monitoring mode (SRM). The MS/MS ion transitions monitored are 409 to 238 for amlodipine, and 260 to 116 for S-(-)-propranolol used as internal standard (IS). The method was validated considering different parameters, such as linearity, precision and accuracy. The limit of quantitation was found to be 0.1 ng/ml for each amlodipine enantiomer.

Amlodipine↗

[Using multislice spiral CT in neuroradiologic imaging].

Multislice computed tomography (MS-CT) was introduced into clinical radiology in 1999 and has shown a significant effect on various indications for computed tomography (CT) imaging in neuroradiology. Technical highlights of this new scanner type are the simultaneous data acquisition by up to four detector rows at present, an accelerated rotation time, and a reduction of the slice thickness to as low as 0.5 mm. These features account for an extended scan area, such as head and neck imaging in polytraumatized patients, detailed contrast-enhanced studies of the cervicocerebral vascular system from the carotid bifurcation to the vertex, as well as cerebral perfusion studies of a larger brain volume with an improved time resolution compared to established CT procedures. In addition, the diagnostic yield of the CT is increased with respect to several applications by reducing common image artefacts at the level of the cervicothoracic junction as well as those caused by metallic implants. Apart from improving the image quality of the primary cross-sectional slices, MS-CT significantly enhances two- and three-dimensional image reconstructions. Radiation protection is an important issue with MS-CT, especially when skull base imaging is considered.

Artifacts↗

DNA sequence recognition of thiazole-containing cross-linked polyamides can be favored.

The binding ability of cross-linked thiazolated polyamides (containing the base sequence-reading elements thiazole(Th)-pyrrole(Py)-pyr-role(Py) and thiazole(Th)-imidazole(Im)-pyrrol(Py) to various DNA dodecamers has been investigated. CD titration experiments at high salt concentration demonstrate that the dimers with a heptanediyl linker (C7 dimer) show a significantly higher sequence specificity than their corresponding monomers. The dimer of Th-Py-Py primarily prefers binding to pure AT sequences and that of Th-Im-Py to the dodecamer sequences containing a GC pair within the central sequence (e.g. AACGTT). Surprisingly, the sequence binding ability is strongly influenced by the presence of a T-A step: e.g. Th-Py-Py has a similar affinity to the sequences TTTAAA and ATCGTA; likewise Th-Im-Py shows a preference for these sequences. The CD results correlate with footprinting data. Related biochemical studies on the effect of polyamides on DNA gyrase activity in vitro show that the C7 dimers most effectively inhibit the enzyme activity compared with the monomers and the natural reference minor groove binder distamycin. The highest inhibitory potency is observed for the Th-Py-Py-dimer. The role of the T-A step in binding of the cross-linked dimer to the minor groove is discussed in light of the sequence recognition of the TATA box binding protein.

AT Rich Sequence↗